1. Field of the Invention
The invention provides reagents and methods for diagnosing kidney disease in a human or animal. In particular, the reagents of the invention comprise immunological reagents, including polyclonal antisera or one or a plurality of monoclonal antibodies, immunologically-specific for proteins and/or peptides in urine, preferably humans with diabetes. The invention provides methods for using these reagents for performing diagnostic and prognostic assays for identifying individuals, particularly humans with diabetes with kidney disease or at risk for kidney disease. The invention also provides kits comprising the diagnostic reagents of the invention for performing the diagnostic methods of the invention.
2. Background of the Related Art
Kidney disease is a significant source of morbidity and mortality in the United States, with more than 100,000 people diagnosed with kidney failure each year. Kidney failure is the final stage of kidney disease, also known as nephropathy. The economic cost of kidney disease is high, costing more than $27 million annually.
The most common cause of kidney failure is diabetes, which affects about 18 million people in the U.S. Diabetes accounts for nearly 45 percent of new cases of kidney failure, and about 30 percent of patients with Type I (juvenile onset) diabetes and 10 to 40 percent of those with Type 2 (adult onset) diabetes will eventually have kidney failure. On average it takes a person with diabetes over 20 years to progress to the end stage.
Kidney failure and nephropathy can occur even when diabetes is controlled. Fortunately, most people with diabetes do not develop nephropathy that is severe enough to cause kidney failure. Unfortunately, the etiological factors behind the development of kidney disease in diabetics are not fully understood, although high blood pressure and high levels of blood glucose increase the risk that a person with diabetes will progress to kidney failure. Diagnostically, diabetics developing kidney disease can have small amounts of the blood protein albumin in the urine, a condition called microalbuminuria. This phenomenon increases as the disease progresses. Conventional quantitative methods for diagnosing kidney disease in diabetics measure the presence of serum albumin in urine, although with varying degrees of sensitivity, accuracy, and precision.
These assays include antibody-based methods such as radioimmunoassay (RIAs), enzyme-linked immunoassays (ELISAs), immunoturbidimetric assays, nephe lometric assays, and non-antibody-based methods such as high performance liquid chromatography (HPLC). Additionally, semi-quantitative methods such as gold immunoassays, latex agglutination, silver dot blot assays, and nigrosin assays are also available. The antibody-based assays suffer from the limitation of “epitopic specificity.” These assays have been developed primarily to detect and quantify urinary albumin and are capable of detecting and quantifying only those albumin moieties that bear antibody-specific epitopes. A fragment or peptide derived from an intact albumin molecule may not be detected by a particular albumin antibody-based assay if the urinary albumin peptide does not bear an epitope specific for the antibodies used in the immunoassays. The semi-quantitative methods of albumin detection are, generally speaking, not accurate and/or sensitive enough for the early detection of the onset of microalbuminuria.
Thus, there remains a need in the art for diagnostic methods for identifying individuals, most preferably diabetics, undergoing early onset, having, or at risk for developing kidney disease.